DESCRIPTION Understanding the dynamic interaction between kinases and phosphates is a critical biochemical mechanism in the control of cytoplasmic signaling that mediates blood cell development. Much of the information passed from cell surface receptor-ligand interaction to the nucleus is transmitted via phosphorylated proteins. We wish to understand the molecular basis and signal transduction pathways responsible for the commitment and differentiation of hematopoietic stem/progenitor cells. We intend to address this question by investigating the role of Shp-2, a protein tyrosine phosphatase, in hematopoiesis. We will determine the role of Shp-2 in mediating the development of a common precursor for hematopoietic and endothelial cells. We will also determine the significance of the ras-Erk kinase pathway in mediating Shp-2 control of hematopoiesis Our ultimate goal is that the findings from these studies will allow for the development of improved and less toxic therapies for human leukemias.